Pharmacokinetic studies on 1-(2-chloroethyl)-3-isobutyl-3-(.BETA.-maltosyl)-1-nitrosourea (TA-077). III. Pharmacokinetics of a new nitrosourea antitumor agent TA-077 in humans (a phase I study).

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…Various pharmacokinetic studies − demonstrated the importance of the maltase enzyme for the biological activity of 555 . Thus, the tissue level of 567 in the kidney, a maltase-rich organ, was always the highest among the organs examined in both guinea pigs and VX-2 tumor-bearing rabbits …”

“…The lower cellular uptake of 555 could explain the difference between its in vitro and in vivo activities since the in vitro test system lacks the maltase enzyme which is essential for the conversion of 555 to the more easily membrane transportable metabolite 567. 453,454 Various pharmacokinetic studies [455][456][457] demonstrated the importance of the maltase enzyme for the biological activity of 555. Thus, the tissue level of 567 in the kidney, a maltase-rich organ, was always the highest among the organs examined in both guinea pigs and VX-2 tumor-bearing rabbits.…”

“…455 Compound 555 was hydrolyzed to 567 by homogenates of guinea pig organs, rabbit VX-2 carcinoma, and rat Yoshida sarcoma, as well as by suspensions of various tumor lines. 456 A phase 1 study 457…”